A5048830611- Heat shock proteins research
- thermodynamics and calorimetric analyses
- ATP Synthase and ATPases Research
- Hippo pathway signaling and YAP/TAZ
- Pharmacological Effects of Natural Compounds
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Enzyme Structure and Function
- Immune Cell Function and Interaction
- Palliative Care and End-of-Life Issues
- Effects of Radiation Exposure
- Toxin Mechanisms and Immunotoxins
- CAR-T cell therapy research
- Meat and Animal Product Quality
- Vector-borne infectious diseases
- Autophagy in Disease and Therapy
- Spectroscopy Techniques in Biomedical and Chemical Research
- Cannabis and Cannabinoid Research
- Childhood Cancer Survivors' Quality of Life
- Protein Structure and Dynamics
- Bee Products Chemical Analysis
- Metabolomics and Mass Spectrometry Studies
- Ethics in medical practice
- Medicinal Plant Pharmacodynamics Research
Klinikum rechts der Isar
2019-2024
Technical University of Munich
2019-2024
Institute of Clinical Cancer Research
2021
Comprehensive Cancer Center Mainfranken
2019-2020
Tulane University
2013
YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators proliferation. Here, we show that ability to activate mitotic gene expression is dependent on Myb-MuvB (MMB) complex, a master regulator genes expressed in G2/M phase cell cycle. By carrying out genome-wide binding analyses, found promotes MMB subunit B-MYB promoters target genes. binds stimulates chromatin association through distal enhancer elements interact with MMB-regulated looping. The cooperation between...
In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in cytosol, but also present it on their plasma membrane a tumor-specific manner. Furthermore, Hsp70-positive actively release Hsp70 small extracellular vesicles with biophysical characteristics exosomes. Due conformational changes lipid environment, most commercially available antibodies fail detect membrane-bound and vesicular Hsp70. To fill this gap assess role circulation...
Although it has been established that cannabidiol (CBD), the major non-psychoactive constituent of cannabis, exerts antitumoral activities, exact mechanism(s) via which tumor cells are killed by CBD not well understood. This study provides new insights into potential mechanisms CBD-induced mutual antagonism apoptosis and macroautophagy using wild type (HCT116 p53wt, LS174T p53wt), knockout p53-/-) mutant (SW480 p53mut) human colorectal cancer (CRC). causes a more pronounced loss in viability...
The Hippo signalling pathway and its central effector YAP regulate proliferation of cardiomyocytes growth the heart. Using genetic models in mice we show that increased embryonal postnatal due to loss Hippo-signaling component SAV1 depends on Myb-MuvB (MMB) complex. Similarly, induced by constitutive active requires MMB. Genome studies revealed MMB an overlapping set cell cycle genes cardiomyocytes. Protein-protein interaction lines with recombinant proteins showed binds directly B-MYB, a...
Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim this study was to identify chaperone- and immune-related biomarkers improve prediction outcome glioblastoma. Depending on its intra- or extracellular localization major stress-inducible heat shock protein 70 (Hsp70) fulfills different tasks. In cytosol Hsp70 interferes pro-apoptotic signaling pathways thereby protects tumor cells from programmed cell death....
The heightened energetic demand increases lactate dehydrogenase (LDH) activity, the corresponding oncometabolite lactate, expression of heat shock proteins (HSPs) and thereby promotes therapy resistance in many malignant tumor cell types. Therefore, we assessed coregulation LDH response with respect to radiation different cells (B16F10 murine melanoma LS174T human colorectal adenocarcinoma). inhibition activity by oxamate or GNE-140, glucose deprivation LDHA/B double knockout (LDH−/−) B16F10...
Strategies to boost anti-tumor immunity are urgently needed treat therapy-resistant late-stage cancers, including colorectal cancers (CRCs). Cytokine stimulation and genetic modifications with chimeric antigen receptors (CAR) represent promising strategies more specifically redirect activities of effector cells like natural killer (NK) T cells. However, these approaches critically dependent on tumor-specific antigens while circumventing the suppressive power solid tumor microenvironment...
The inhibition of heat shock protein 90 (Hsp90) a molecular chaperone for multiple oncogenic client proteins is considered as promising approach to overcome radioresistance. Since most Hsp90 inhibitors activate HSF-1 that induces the transcription cytoprotective and tumor-promoting stress such Hsp70 Hsp27, combined consisting knockdown (k.d.) was investigated. A specific k.d. achieved in H1339 lung cancer cells using RNAi-Ready pSIRENRetroQ vectors with puromycin resistance. inhibitor...
The major stress-inducible protein Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending its intracellular or membrane localization, either promotes growth serves as a target for natural killer (NK) cells. kinetics (mHsp70) density human glioma (U87) was studied after different irradiation doses to define optimal therapeutic window Hsp70-targeting NK To maintain exponential...
Abstract Background An enhanced aerobic glycolysis (“Warburg effect”) associated with an increase in lactic acid the tumor microenvironment contributes to aggressiveness and resistance radiation chemotherapy. We investigated radiation- chemo-sensitizing effects of nonsteroidal anti-inflammatory drug (NSAID) diclofenac different cancer cell types. Methods The a non-lethal concentration was on c-MYC Lactate Dehydrogenase (LDH) protein expression/activity Heat shock Protein (HSP)/stress...
As overexpression and membrane localization of stress proteins together with high lactate levels promote radioresistance in tumor cells, we studied the effect Hsp90 inhibitor NVP-AUY922 on cytosolic expression heat shock (HSPs) radiosensitivity murine melanoma (B16F10) human colorectal (LS174T) wildtype (WT) dehydrogenases A/B double knockout (LDH-/-) cells. Double for LDHA/B has been found to reduce as well HSP levels, whereas treatment stimulates synthesis Hsp27 Hsp70, but does not affect...
The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending its intracellular or membrane localization, either promotes growth serves as a target for NK cells. kinetics (mHsp70) density human glioma (U87) was studied after different irradiation doses to define optimal therapeutic window Hsp70-targeting To maintain exponential phase during cultivation period...
Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology utility tumor biomarkers animals such as cats pigs. In this study, free blood with spontaneously occurring tumors detected a commercial (R&D Systems). Sub-analysis groups revealed that...
Abstract Background An enhanced aerobic glycolysis (Warburg effect) associated with an increase in lactic acid the tumor microenvironment contributes to aggressiveness and resistance radiation chemotherapy. We investigated radiation- chemo-sensitizing effects of nonsteroidal anti-inflammatory drug (NSAID) diclofenac different cancer cell types. Methods The a non-lethal concentration was on MYC expression, lactate dehydrogenase (LDH) activity heat shock protein response human colorectal...
Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. Recombinant heat shock protein 70 (Hsp70) and IL-2 stimulate cytolytic activity NK cells against large variety highly aggressive human tumor presenting Hsp70 on their cell surface. Therefore, intra- extracellular expression was determined gliomas together activatory receptors which are known to interact membrane-bound (mHsp70). All mHsp70-positive high grade overexpress...
Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim this study was to identify immune-related biomarkers that more effectively predict outcome glioblastoma. Since heat shock protein 70 (Hsp70) and IL-2 are known increase expression activatory NK cell receptors, recognizing aggressive human tumor cells present Hsp70 on their surface, extracellular levels were determined glioma patients together receptors. All...
ABSTRACT The Hippo signalling pathway and its central effector YAP regulate proliferation of cardiomyocytes growth the heart. Using genetic models in mice we show that increased due to loss Hippo-signaling component SAV1 depends on Myb-MuvB (MMB) complex. Similarly, postnatal induced by constitutive active requires MMB. Genome studies revealed MMB an overlapping set cell cycle genes cardiomyocytes. We find binds directly B-MYB, a subunit MMB, manner dependent WW domains PPXY motif B-MYB....
Abstract Therapy (radiation) resistance can, inter alia, be caused by an increased lactate dehydrogenase (LDH) activity, elevated concentrations of the oncometabolite and overexpression anti-apoptotic heat shock proteins (HSPs). In this study we aimed to break radioresistance targeting cancer metabolism. We could show, for first time, that metabolism response are co-regulated in two cell systems (murine B16F10 melanoma cells, human LS174T colorectal adenocarcinoma cells). A CRISPR/Cas9...
In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in cytosol, but also present it on their plasma membrane a tumor-specific manner. Furthermore, membrane-Hsp70 positive actively release Hsp70 into lipid microvesicles termed exosomes blood. Due conformational changes environment, most commercially available antibodies fail detect membrane-bound and exosomal Hsp70. To fill this gap assess role circulation as potential...